Virus-induced interferon alpha production by a dendritic cell subset in the absence of feedback signaling in vivo

• Published in: The Journal of experimental medicine Vol. 195; no. 4; pp. 507 - 516
• Main Authors: Barchet, Winfried, Cella, Marina, Odermatt, Bernhard, Asselin-Paturel, Carine, Colonna, Marco, Kalinke, Ulrich
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 18-02-2002
• Subjects: a-Interferon; Animals; Cells, Cultured; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Dendritic Cells - virology; DNA-Binding Proteins - metabolism; Feedback, Physiological; Fibroblasts - metabolism; Fibroblasts - virology; Flow Cytometry; Gene Deletion; Gene Expression Regulation - drug effects; In Situ Hybridization; Interferon Regulatory Factor-7; Interferon-alpha - biosynthesis; Interferon-alpha - genetics; Interferon-alpha - metabolism; Interferon-beta - metabolism; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Original; Poly I-C - pharmacology; Receptor, Interferon alpha-beta; Receptors, Interferon - deficiency; Receptors, Interferon - genetics; Receptors, Interferon - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - drug effects; Spleen - metabolism; Spleen - pathology; Time Factors; Ultraviolet Rays; Vesicular stomatitis Indiana virus - physiology; Vesicular stomatitis virus
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20011666

An effective type I interferon (IFN-alpha/beta) response is critical for the control of many viral infections. Here we show that in vesicular stomatitis virus (VSV)-infected mouse embryonic fibroblasts (MEFs) the production of IFN-alpha is dependent on type I IFN receptor (IFNAR) triggering, whereas in infected mice early IFN-alpha production is IFNAR independent. In VSV-infected mice type I IFN is produced by few cells located in the marginal zone of the spleen. Unlike other dendritic cell (DC) subsets, FACS((R))-sorted CD11c(int)CD11b(-)GR-1(+) DCs show high IFN-alpha expression, irrespective of whether they were isolated from VSV-infected IFNAR-competent or -deficient mice. Thus, VSV preferentially activates a specialized DC subset presumably located in the marginal zone to produce high-level IFN-alpha largely independent of IFNAR feedback signaling.